1 GOOD MORNING! BONJOUR! GOEDEMORGEN!
Dec 14, 2015
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An Introduction to certain aspects of the US FDA
Murray M. Lumpkin, MDDeputy Commissioner
International ProgramsUS Food and Drug Administration
Belgian Trade DelegationWashington28 June 2011
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FDA – Belgium - Europe
Long history of interactionsConfidentiality arrangements with:
Belgian Scientific Institute of Public Health Belgian Federal Agency for Medicines and Health Products Quality of Medicines & HealthCare (EDQM)Health and Consumer Protection Directorate-General (DG SANCO) EMA EFSA
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Confidentiality Arrangements
Legal Framework to share:Commercial confidential informationPre-decisional informationInvestigative – compliance informationPharmacovigilance data, reportsNOT Trade Secret information
NO requirement to exchange anything
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FDA = Federal Drug AdministrationFood and Drug AdministrationPart of Department (Ministry) of Health and Human Services Secretary (Minister) part of President’s cabinet (Kathleen Sibelius)Commissioner of Food and Drugs – (Dr Margaret Hamburg) appointed by President, confirmed by Senate, responsible to Secretary – politicals / career CDC, NIH, others also part of DHHS (FDA is the only regulatory body in DHHS)Our secretary & commissioner are not part of our Congress (not a parliamentary system)
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FDA - Components~12,000 employees (~7500 in Washington)Office of the Commissioner (OC)Office of Regulatory Affairs (ORA) (inspectorate/enforcement)Center for Devices and Radiologic Health (CDRH)Center for Veterinary Medicine (CVM)Center for Food Safety and Applied Nutrition (CFSAN)National Center for Toxicologic Research (NCTR)Center for Tobacco ProductsCenter for Biologics Evaluation and Research (CBER)Center for Drug Evaluation and Research (CDER)
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Two medicines laws
U.S. Public Health Service Act (1902)Most biologically derived human medicines
Biosimilars (2010)
Federal Food, Drug, and Cosmetic Act (1938)Most chemically derived human and animal medicines
Generic Drugs (1984)
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NEW MEDICINE DEVELOPMENT
Dis
cove
ry /
Scr
een
ing
SynthesisandPurification
Animal Testing
Pre-clinicalResearch
IND Clinical Studies
Short-term
Long-term
Phase 1
Phase 2
Phase 3
MA
A R
evie
w
Pos
t-au
thor
isat
ion
MA“NDA”
AP
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IND PROCESS(IND = Investigational New Drug)
Submit IND application before 1st clinical study in the US (no matter what “phase” the first study is)
Regulatory vehicle under which all investigational trials are overseen in the USAAll animal data, previous clinical data outside USA (if any), development plan, and first protocol with special emphasis on any safety concerns and manufacturing process for clinical trials suppliesMake case for why it is reasonable to proceed into humans at this point and why the plan for safety monitoring is adequateInclude IRB (ethics committee) oversight information (name)
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IND PROCESSAfter 1st submission – must wait 30 calendar days.
If nothing heard from FDA, may proceed on day 31. Do not need to wait for authorising letter. In fact, there is no “authorising letter”
Subsequent submissions are all “notifications”. Do not need to wait to start trial, simply notify.
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IND PROCESSFDA can place any trial (or part of a trial) on “hold” at any time
“Hold” means trial may not proceed and, if started, no further patients may be enrolled
If application not completeIf FDA does not believe it is reasonably safe to proceedIf FDA does not believe company is properly monitoring for potential safety problemsIf FDA believes trial design puts patients at risk for no scientific purpose (vs not going to answer the question the company wants to have answered)
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WHY DO WE DO THIS?Promote and Protect Public health – clinical trials are how we initially learn about the safety and efficacy of new products
Need independent oversight to help assure that subjects are not put at unreasonable risk and not put into trials from which we cannot reasonably expect to learn something scientifically relevant
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WHY DO COMPANIES ENGAGE WITH US FDA
DURING DEVELOPMENT
Submissions are required
Essentially all engage much more than minimally required
No direct cost for such meetings
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FDA / SPONSORS DURING DRUG DEVELOPMENT
Interact with sponsors to maximise efficiency and scientific robustness of their drug development program
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VERY IMPORTANT:PRE-IND / END OF PHASE 2Reach Understanding of Development Goals and ImplementationTrial designs / Where to do themEvaluability CriteriaDefine a “Win”
Characterise ProductIndications, Dosing Regimen(s)Major Safety ParametersManufacturing Issues
Possible modifications with time
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SPECIAL PROTOCOLSCarcinogenicityStabilityP3 trials that will be primary data for an efficacy claim
Performance goal: 45 daysWritten agreements binding except when science changes
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When can a product be authorised?
When the data show that the demonstrated benefits outweigh the known risks for the intended population when used as directed
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EARLY ACCESS INITIATIVESD
isco
very
/ S
cree
nin
g
SynthesisandPurification
Animal Testing
Pre-clinicalResearch
IND subm
Clinical Studies
Short-term
Long-term
Phase 1
Phase 2
Phase 3
MA
A R
evie
w
Pos
t-au
thor
isat
ion
AP
Subpart E:Submit MA here
Accelerated Approval:
Priority ReviewFast Track-Rolling Review
Treatment IND
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US - EU COMPARISON(Nomenclature)
United StatesPriority Review
Accelerated Approval (Subpart H)
Subpart E
Fast Track
European UnionFast Track
Conditional Approval
Approval under special circumstances
No equivalent